Cardiovascular disease (CVD) causes 17.7 million deaths annually worldwide and is therefore a major health burden to our society. Over the last century, CVD treatment has greatly improved. The discovery of cholesterol lowering drugs has led to a strongly improved treatment of CVD. However, atherosclerosis, the main underlying cause of CVD, is not solely a cholesterol-driven disease. Recently a large human study showed that inflammation is also an important factor in the development of atherosclerosis. Understanding the factors that contribute to inflammation is therefore of great importance. The gut microbiota is one such factor that has recently been linked to cardiovascular disease and inflammation. However, it is unknown whether alterations in microbiota composition can contribute to CVD development and if interactions between the gut immune barrier, diet and gut microbiota can affect systemic inflammation and atherosclerosis. In this thesis, we used mouse models to understand how the interaction between the diet, gut microbiota and intestinal immune barrier contributes to systemic inflammation and atherosclerosis. Our studies show a causal role of the gut microbiota in the development of systemic inflammation and atherosclerosis. Furthermore, our studies indicate a protective role of the gut immune system and in particular of antimicrobial against development of CVD. Thus our studies indicate that the gut microbiota and the gut immune system may be interesting future targets for the treatment of CVD.
|Qualification||Doctor of Philosophy|
|Place of Publication||[Groningen]|
|Publication status||Published - 2019|